Within the past several decades, great advances have been made in the diagnosis and treatment of vitreoretinal diseases. Advances in laser technology, and vitreoretinal surgical techniques, have significantly improved the prognosis of numerous retinal conditions including diabetic retinopathy, macular degeneration, and retinal detachment. As the pathophysiology of these and many other vitreoretinal diseases is also becoming more clearly understood, a host of potential pharmacological agents is currently under investigation.
In addition to the numerous antibiotic, antiviral, and antifungal agents currently used to treat infections of the retina and vitreous, many antiinflammatory and anticancer drugs have been shown to be useful in treating diseases such as proliferative vitreoretinopathy. As the role of growth factors involved in diabetic retinopathy, macular degeneration, and other retinal degenerations is elucidated, new classes of agents have been found to be of possible benefit, including growth factors themselves, blocking antibodies to growth factors, antisense oligonucleotides, and even gene therapy with growth factor inserts.
Unfortunately, the delivery of drugs to the retina is often problematic. Most agents given topically to the eye (in the form of eye drops) do not penetrate through the anterior segment of the eye well enough to reach the vitreous or retina in therapeutic concentrations. Medications can be given orally or intravenously, but the blood vessels within the retina (and other parts of the central nervous system) are relatively impermeable to many agents. Furthermore, these drugs may have significant systemic side effects on other organs of the body. Drugs can be directly injected into the vitreous cavity, via a needle passed through the pars plana, and this technique is currently employed to combat certain severe, sight-threatening infections. However, this procedure itself entails certain risks, such as infection, bleeding, cataract formation, and retinal detachment. Furthermore, the majority of the injected drug is often cleared from the vitreous cavity within several days, necessitating multiple injections for prolonged treatment.
Accordingly, devices have been developed for improving the introduction of drugs to the vitreal cavity. One such device is a biodegradable polymer designed to be injected into the vitreous cavity where it slowly releases drug as it dissolves. A similar drug-containing polymer has been developed which is made in the shape of a tack or plug to be surgically inserted into the eyewall at the pars plana so that it projects into the vitreous cavity. Liposomes containing pharmacological agents have been developed to slowly release the agent after injection into the vitreous cavity. Another device is a plastic pellet which contains a retinal drug (ganoclovir) and is sutured inside of the vitreous cavity where the drug slowly dissolves into the cavity.
Although such devices as those briefly referred to above are apparently effective in delivering drugs into the vitreous cavity, they have significant disadvantages. First, all of these devices contain a certain amount of drug which when expended cannot be replenished without repeating the surgical implantation or intravitreal injection. Although these different devices can release drugs for weeks to months (or in the case of the plastic pellet, almost one year), certain indications for intravitreal drug administration require extended or lifetime therapy. Therefore, multiple procedures are often required and are highly undesirable.
Secondly, the device with the longest release rate, the plastic pellet of ganiclovir, requires a very large eyewall incision (5 mm) to implant due to its large size. Although the other devices can be implanted or injected through a smaller incision (1 mm or less), those that are injected freely into the vitreous cavity instead of anchored to the eyewall can migrate within the eye and come in direct contact with the retina where they can block vision or release high local concentrations of drug which could potentially prove toxic to delicate retinal tissue.
Third, many pharmacological agents cannot easily and effectively be incorporated into biodegradable polymers. Furthermore, many potential pharmacological agents would not remain stable for extended periods of time in the vitreous cavity. Therefore, there is a significant limitation to what pharmacological agents can be administered via the slow release devices currently available.
Fourth, since the plug or pellet is in essence the drug itself, treatment is limited to this drug, so that another surgery or procedure is required to change it if administration of a different drug is desired.